Excellent outcome of allogeneic bone marrow transplantation for Fanconi anemia using fludarabine-based reduced-intensity conditioning regimen

Fanconi anemia (FA) is a disorder characterized by developmental anomalies, bone marrow failure and a predisposition to malignancy. It has recently been shown that hematopoietic stem cell transplantation using fludarabine (FLU)-based reduced-intensity conditioning is an efficient and quite safe therapeutic modality. We retrospectively analyzed the outcome of bone marrow transplantation (BMT) in eight patients with FA performed in two institutes between 2001 and 2011. There were seven females and one male with a median age at diagnosis = 4.5 years (range 2-12 years). The constitutional characteristics associated with FA, such as developmental anomalies, short stature and skin pigmentation, were absent in three of the patients. One patient showed myelodysplastic features at the time of BMT. All patients received BMT using FLU, cyclophosphamide (CY) and rabbit anti-thymocyte globulin (ATG) either from a related donor (n = 4) or an unrelated donor (n = 4). Acute graft-versus-host disease (GVHD) of grade I developed in one patient, while chronic GVHD was not observed in any patient. All patients are alive and achieved hematopoietic recovery at a median follow-up of 72 months (range 4-117 months). BMT using FLU/low-dose CY/ATG -based regimens regardless to the donor is a beneficial therapeutic approach for FA patients.     

Childhood acute myeloid leukemia with bone marrow eosinophilia caused by t(16;21)(q24;q22)

Acute myeloid leukemia with abnormal bone marrow eosinophilia (AML-M4Eo) is often reported in core binding factor (CBF) leukemia, with translocations such as inv(16)(p13q22), t(16;16)(p13;q22) or t(8;21)(q22;q22); however, it is rarely reported with t(16;21)(q24;q22), which produces the RUNX1-CBFA2T3 (AML1-MTG16) chimera. The similarity between this chimera and RUNX1-RUNXT1 (AML1-MTG8) by t(8;21)(q22;q22) remains controversial. Adult leukemia with t(16;21)(q24;q22) was primarily therapy related, and shows poor prognosis; however, pediatric AML with this translocation was quite rare and tended to be de novo AML. We present here a 4-year-old boy with de novo AML-M4Eo and t(16;21)(q24;q22). He received chemotherapy and survived for more than 70 months without transplantation. We speculated that pediatric AML with t(16;21)(q24;q22) showed favorable prognosis, as with t(8;21)(q22;q22).     

Endoscopic approach through the minor papilla for the management of pancreatic diseases

AIM: To clarify the efficacy and safety of an endoscopic approach through the minor papilla for the management of pancreatic diseases.METHODS: This study included 44 endoscopic retrograde cholangiopancreatography (ERCP) procedures performed in 34 patients using a minor papilla approach between April 2007 and March 2012. We retrospectively evaluated the clinical profiles of the patients, the endoscopic interventions, short-term outcomes, and complications.RESULTS: Of 44 ERCPs, 26 were diagnostic ERCP, and 18 were therapeutic ERCP. The most common cause of difficult access to the main pancreatic duct through the major papilla was pancreas divisum followed by distortion of Wirsung’s duct. The overall success rate of minor papilla cannulation was 80% (35/44), which was significantly improved by wire-guided cannulation (P = 0.04). Endoscopic minor papillotomy (EMP) was performed in 17 of 34 patients (50%) using a needle-knife (13/17) or a pull-type papillotome (4/17). EMP with pancreatic stent placement, which was the main therapeutic option for patients with chronic pancreatitis, recurrent acute pancreatitis, and pancreatic pseudocyst, resulted in short-term clinical improvement in 83% of patients. Mild post-ERCP pancreatitis occurred as an early complication in 2 cases (4.5%).CONCLUSION: The endoscopic minor papilla approach is technically feasible, safe, and effective when the procedure is performed in a high-volume referral center by experienced endoscopists.     

Amino acid sequence of the T4 DNA helix-destabilizing protein.

The primary structure of the T4 single-stranded DNA-binding protein coded by gene 32 has been determined by manual and autoated sequencing of peptides derived from partial proteolysis, cyanogen bromide cleavage, and digestion with trypsin, chymotrypsin, and staphylococcal protease. Tryptic digestion of citraconylated or succinylated gene 32 protein yields five peptides containing 4, 27, 42, 65, and 163 residues, which can be separated by Sephadex chromatography. Each of the tryptic peptides was subjected to automated sequencing and, if necessary, more extensive cleavage. The intact protein contains 301 amino acids, has a molecular weight of 33,487, and can be specifically cleaved at lysines 21 and 253 by limited trypsin digestion. Previous studies have shown that the "B" region (residues 1-21), which has a charge of +4, is important for the protein-protein interactions involved in gene 32 protein self-association and cooperaive binding to single-stranded DNA. The "A" region (residues 254-301) has been implicated in controlling the helix-destabilizing "activity" of gene 32 protein and in interacting with other T4 DNA replication proteins. The A region has a charge of -10 and, in addition, contains two unusual stretches of four serine residues separated by glycine 284. The region between positions 73 and 115 contains 75% of the tyrosine residues and may be important for DNA binding.     

Spontaneous improvement of hematologic abnormalities in patients having juvenile myelomonocytic leukemia with specific RAS mutations

Of 11 children with juvenile myelomonocytic leukemia (JMML) carrying RAS mutations (8 with NRAS mutations, 3 with KRAS2 mutations), 5 had a profound elevation in either or both the white blood cells and spleen size at diagnosis. Three patients had no or modest hepatosplenomegaly and mild leukocytosis at presentation but subsequently showed a marked increase in spleen size with or without hematologic exacerbation, for which nonintensive chemotherapy was initiated. The other three patients with NRAS or KRAS2 glycine to serine substitution received no chemotherapy, but hematologic improvement has been observed during a 2- to 4-year follow up. In the third group, all hematopoietic cell lineages analyzed had the RAS mutations at the time of hematologic improvement, whereas DNA obtained from the nails had the wild type. Additionally, numbers of circulating granulocyte-macrophage progenitors were significantly reduced during the clinical course. Thus, some patients with JMML with specific RAS mutations may have spontaneously improving disease.     

Hemodynamic management of LOS using prolonged VA bypass circulatory assist]

The authors managed five LOS patients using prolonged V-A bypass circulatory assist. Maximum CVP values were under 12 mmHg in three survivors, and 17 mmHg and 20 mmHg in two nonsurvivors. Maximum PCWP values were under 14 mmHg in survivors, and 19 mmHg and 20 mmHg in nonsurvivors. Dopamine was administrated in all cases and norepinephrine was administrated at a rate of less than 0.3 microgram.kg-1.min-1 in survivors, and in two nonsurvivors, norepinephrine was used at a rate of 0.36 and 1.2 micrograms.kg-1.min-1. Before and after disconnection of V-A bypass, the bypass flow of the three survivors were under 1.0 l.min-1 just before disconnection, and immediately after it, the preload did not increase, and the dose of administrated catecholamine increased. V-A bypass time intervals of the three survivors were 71, 42 and 87 hours, and those of the two nonsurvivors were 71 and 43 hours. Maximum bypass flow rate was above 40ml.kg-1.min-1 in four of five patients. The authors discussed the management of the patients' heart and of the V-A bypass machine during the prolonged V-A bypass circulatory assist.